Abstract
Purpose :
We have recently shown that the distal region of the conventional outflow pathway is innervated with peripheral, autonomic, and sensory nerve fibers. Presence of synaptic structures in these areas indicated a neural control paradigm of the distal outflow region. Based on this, we assessed the role of dopamine D1 and D2 receptors on regulation of intraocular pressure (IOP) in normotensive C57BL/6J mice.
Methods :
Localization of D1 and D2 receptors in the conventional outflow region of C57BL/6J mice was evaluated using immunohistochemistry and confocal microscopy. C57BL/6J mice eyes were topically treated with various concentrations of dopamine receptor antagonist eticlopride (1-10 mM) or agonists SKF38393 and bromocriptine (0.03, 0.3, 3.3 mM) once daily for up to 5 days. IOP was measured using a handheld rebound tonometer 3 times daily at times corresponding to 1, 4 and 23 h post treatment. Daily IOP was calculated as average of the three readings and expressed as mean ± standard deviation.
Results :
Mouse eyes showed extensive localization of dopamine D1 and D2 receptors to the trabecular meshwork, Schlemm’s canal and distal vessels. Treatment with 5 mM eticlopride for 5 days elevated IOP by 26.8 ± 2.3 % compared to vehicle controls. In contrast, IOP was lowered by dopamine receptor agonists SKF38393 and bromocriptine in a dose dependent manner. At doses of 0.3 and 3.3 mM, both SKF38393 and bromocriptine showed significant IOP reduction (SKF38393, 0.3 mM, -19.5 ± 2.1 %, 3.3 mM, -19.3 ± 1.5 %; bromocriptine, 0.3 mM, -19.1 ± 0.6 %, 3.3 mM, -17.3 ± 1.1 %; p<0.05). No change was seen at 0.03 mM dose (SKF38393, -1.6 ±1.2 %, p=0.1; bromocriptine, -1.2 ± 1.1 %, p=0.1).
Conclusions :
Dopamine D1 and D2 receptors are involved in IOP homeostasis in normotensive mice. Agonists of D1 and D2 receptors may have strong potential as ocular hypotensive agents.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.